Separating and purifying organic compounds from mixtures of substances is still, in many sectors, a problem which has not been solved satisfactorily. Removing certain impurities or separating mixtures of complex mixtures of substances requires specific methods. The success of the separation depends substantially on the structure of the compound to be removed; in particular for compounds of similar structure, specially adapted, frequently highly expensive, methods are required. Thus, for example, for partial esters of glycerol with higher fatty acids such as monoglycerides, scarcely any simple and effective methods are available for purification.
Monoglycerol esters, for example of oleic acid, palmitic acid, stearic acid, are the focus of economic interest. They have emulsifying, stabilizing, plasticizing and thickening properties and are used, for example, as emulsifiers for doughs, for sweeteners and baking aids, margarine and ice cream in the food industry (labeling for mono- and diglycerides of fatty acids: E 471). They are also used, for example, as lubricants in the plastics processing (for example: glycerol monostearate).
Reacting monoglycerides with acetic acid produces acetylated, liquid to waxy monoglycerides (acetoglycerides) which, owing to their good compatibility with active pharmaceutical compounds and their physiological safety, are used in foods as protective films, in cosmetics and pharmaceutical products.
Pharmaceutical applications particularly are increasingly becoming of public interest recently. For instance monoglycerides are described as PPAR activators (PPAR: Peroxisome Proliferator Activated Receptor) which are suitable for ameliorating overweight and diabetes (JP-A 2001-354558).
Monoglycerides are generally produced by transesterifying triglycerides with glycerol, or by reacting glycerol with corresponding fatty acids. However, the currently widespread lipase reaction (KR-A 127510, JP-A 09-268299) is also being used to synthesize monoglycerides and diglycerides. Usually, mixtures of triglycerides, diglycerides, monoglycerides, free fatty acids and glycerol are obtained, and in virtually all cases a purification is necessary, that is to say separation and enrichment of the monoglycerides from the complex mixtures.
Frequently distillation methods are used for this (Bornscheuer et al., Enzymes in Lipid Modification Ed. U. T. Bornscheuer, Wiley-VCH, 2000), which, however, owing to the high temperatures (T>200° C.) required in these methods, can only be used with restrictions, since acyl migrations or even the destruction of the desired products, in particular in the case of compounds sensitive to oxidation are the consequence (Naohiro et al. U.S. Pat. No. 6,025,384, Mares et al. CS-A 864520). This requires complex downstreaming to produce pure monoglycerides (Bornscheuer et al. see above).
A further current method for cleaning up is isolation via cold crystallization, since monoglycerides generally have different melting points from the corresponding tri-glycerides, diglycerides and free fatty acids. In some cases this successfully removes selectively the monoglycerides from diglycerides, triglycerides and other constituents.
However, this method is not universally usable, since non-uniform mixtures are difficult to work up, for example monoglycerides containing differing fatty acids, or monoglycerides which are present as regioisomers. The prochirality of many monoglycerides also plays a significant role. For instance, the melting points of rac-1-palmitoylglycerol (D,L-alpha-glycerol monopalmitate, approximately +74.9° C.) and 3-palmitoyl-sn-glycerol (L-alpha-glycerol monopalmitate, +71.1° C.) differ. The melting point of 2-monopalmitate (approximately +68° C.) is likewise different. The circumstance that the melting point is significantly affected by the fatty acid group makes selective crystallization difficult, in particular from mixtures.
In practice, the only separation which is successful is via crystallization of monoglycerides which bear fatty acids having more than 12 carbon atoms. Furthermore, the separation is considerably more difficult in the case of monoglycerides containing unsaturated fatty acids, for example oleic acid (18:1). In the case of polyunsaturated fatty acids the separation (crystallization) is virtually no longer successful.
Kang et al. (KR-A 94-6988) describe the synthetic preparation of monoglycerides and subsequent purification by means of solvent extraction.
Kolstad et al. describe a method for purifying monoglycerides by means of liquid-liquid extraction methods (U.S. Pat. No. 5,959,128).
Purification by column chromatography is described by Mekawa et al. (JP-A 61-166399). He successfully separates, in small yields, alpha- and beta-monoglycerides with the use of the ion-exchange material XAD, a synthetic-resin-based ion exchanger. Generally, the use of silica gels as ion-exchange material is not very suitable, since, owing to the acid behavior of many silica gels, an acyl migration can be catalyzed and thus purification opposed.
The PCT application 02/06158 describes an extraction method by selective complexation to a silver-ion-loaded cation exchanger and subsequent decomplexation to produce unsaturated, possibly derivatized, compounds from mixtures. This method is restricted to compounds containing highly unsaturated components, for example unsaturated long-chain fatty acids.
None of the known processes leads to satisfactory yields and sufficient selectivities in the purification of mixtures of compounds of the type described at the outset.
It is thus an object of the present invention to provide a method which permits the production of saturated organic compounds containing functional groups from mixtures which comprise these saturated organic compounds containing functional groups and also one or more other organic compounds. This method should make possible a quantitatively sufficient purification, a simplification of the method and an economic design of same. Furthermore, the method should be selective in order to make possible, for example, the separation of compounds which differ only slightly structurally.